Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure.

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation

Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring

Urea Memory: Transient Cell Exposure to Urea Causes Persistent Mitochondrial ROS Production and Endothelial Dysfunction

Urea at post-dialysis levels induces increased ROS in a number of cell types. The aim of this study was to determine whether urea-induced production of ROS remains elevated after urea is no longer present, and, if it does, to characterize its origin and effects. Human arterial endothelial cells were incubated with 20 mM urea for two days, and then cells were incubated for an additional two days in medium alone. Maximal ROS levels induced by initial urea continued at the same level despite urea being absent. These effects were prevented by either MnSOD expression or by Nox1/4 inhibition with GKT13781. Sustained urea-induced ROS caused a persistent reduction in mtDNA copy number and electron transport chain transcripts, a reduction in transcription of mitochondrial fusion proteins, an increase in mitochondrial fission proteins, and persistent expression of endothelial inflammatory markers. The SOD-catalase mimetic MnTBAP reversed each of these. These results suggest that persistent increases in ROS after cells are no long exposed to urea may play a major role in continued kidney damage and functional decline despite reduction of urea levels after dialysis

Compositional and diversity comparisons between the palynological records of the Neogene (Solimões Formation) and Holocene sediments of Western Amazonia

Western Amazonia underwent dramatic changes in its landscape and environments during the Neogene, which led to its extant, hyperdiverse, tropical rainforest. Although the palynological fossil record has been the most useful proxy for understanding the history of the Amazonian biome, the floristic composition and diversity of the Neogene and the present Amazonian environments have never been thoroughly compared. In this work, we present preliminary comparisons of the pollen content of a Miocene core from the Solimões Formation in western Amazonia (Brazil) with the pollen content of Holocene sediments from flooded environments (várzeas and lake margins) near the Miocene site. We found a total of 463 pollen and spore types (Miocene, n = 284; Holocene, n = 231), only 52 of which were shared. The Holocene flooding environments displayed distinct palynological signals; both the Holocene and Miocene palynofloras have pollen primarily sourced from the local, flooded environments, with no significant differences in within-sample pollen diversity. The Holocene palynoflora was more heterogeneous in composition than the Miocene palynoflora, probably because the Miocene wetlands (the Pebas System) were highly homogeneous at a continental scale, far more than modern western Amazonia, thus implying that the spatial vegetation turnover was much lower than in modern ecosystems. © 2019, © 2019 AASP–The Palynological Society

Sex and Gender-Related Differences in the Outcome of Total Hip Arthroplasty: A Current Concepts Review

Background and Objectives: Sex and gender-related differences may influence the outcome of patients undergoing total hip arthroplasty (THA). The present paper aims to depict the importance of sex and gender-related issues in the perioperative management of patients undergoing THA to improve clinical outcomes and prevent postoperative complications. Materials and Methods: From January 2002 to August 2022, OVID-MEDLINE, EMBASE, SCOPU S, Web of Science, Google Scholar, and PubMed were searched to identify relevant studies for further analysis. The search strategy included the following terms: ((“gender-related differences” [MeSH Terms] OR “sex-related differences” [All Fields]) OR (“gender indicators” [MeSH Terms] OR “sex” [All Fields])) AND (“total hip arthroplasty” [MeSH Terms] OR (total hip replacement [All Fields])). Results: Twenty-eight papers were included in this current concepts review. Sex and gender-related differences were analyzed with regard to the following points: (1) surgical approach, robotic surgery, scar cosmesis, and implant choice; (2) postoperative clinical outcome and complications; (3) sexual activity after THA; and (4) psychological status and daily functional requirements. The data analysis showed that female patients need more specific attention in the preoperative, intraoperative, and postoperative phases to improve clinical and functional outcomes, reduce complications risk, and manage patient satisfaction. Conclusions: THA outcomes may be influenced by sex and gender-related factors which should be carefully assessed and addressed in patients undergoing surgery to improve the postoperative outcomes of patients’ satisfaction and reduce postoperative complications that can differ between the two sexes

Ancient Grain Flours with Different Degrees of Sifting: Advances in Knowledge of Nutritional, Technological, and Microbiological Aspects

Ancient grains have gained considerable attention in recent years, as some research suggests they may be healthier than modern wheat. The present study aims to evaluate the chemical, rheological, and microbiological features of three Southern Italian cultivated ancient wheat varieties: Risciola, Carosella, and Saragolla. ATR-FTIR analyses were performed on the finely ground grain samples of the three varieties. The selected grains were ground with a stone mill, and different sifting degrees (whole—100%, type 1—80%, and type 0—72%) were evaluated. The flours showed a good nutritional profile, a higher amylose/amylopectin ratio, and a lower glycemic index than the literature. The gluten index of the samples was in the range 2.6–28.9%, and the flours can be classified as weak, having a value <30%. The farinographic test showed a short development time, low dough stability, a high softening degree, and water absorption, which increased with the degree of sifting. Microbiological analyses performed on flours from ancient grains at different degrees of sifting show their safety, according to their microbiological parameters, which fall within the legal microbiological requirements established by the European Commission Regulation (EC)

Urea Memory: Transient Cell Exposure to Urea Causes Persistent Mitochondrial ROS Production and Endothelial Dysfunction

Urea at post-dialysis levels induces increased ROS in a number of cell types. The aim of this study was to determine whether urea-induced production of ROS remains elevated after urea is no longer present, and, if it does, to characterize its origin and effects. Human arterial endothelial cells were incubated with 20 mM urea for two days, and then cells were incubated for an additional two days in medium alone. Maximal ROS levels induced by initial urea continued at the same level despite urea being absent. These effects were prevented by either MnSOD expression or by Nox1/4 inhibition with GKT13781. Sustained urea-induced ROS caused a persistent reduction in mtDNA copy number and electron transport chain transcripts, a reduction in transcription of mitochondrial fusion proteins, an increase in mitochondrial fission proteins, and persistent expression of endothelial inflammatory markers. The SOD-catalase mimetic MnTBAP reversed each of these. These results suggest that persistent increases in ROS after cells are no long exposed to urea may play a major role in continued kidney damage and functional decline despite reduction of urea levels after dialysis